Evidence map›Paper›PMID 26089541›Full record

ArticleJournal of the National Cancer Institute2015

E2F8 as a Novel Therapeutic Target for Lung Cancer.

Sin-Aye Park, James Platt, Jong Woo Lee, Francesc López-Giráldez, Roy S Herbst, Ja Seok Koo

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

72 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Sin-Aye ParkSection of Medical Oncology, Department of Internal Medicine (SAP, JWL, RSH, JSK) and Translational Research Program (RSH, JSK), Yale Comprehensive Cancer Center, Departments of Pathology and Medical Oncology (JP), Yale School of Medicine, New Haven, CT; Yale Center for Genome Analysis, Yale University, Orange, CT (FLG).
James PlattSection of Medical Oncology, Department of Internal Medicine (SAP, JWL, RSH, JSK) and Translational Research Program (RSH, JSK), Yale Comprehensive Cancer Center, Departments of Pathology and Medical Oncology (JP), Yale School of Medicine, New Haven, CT; Yale Center for Genome Analysis, Yale University, Orange, CT (FLG).
Jong Woo LeeSection of Medical Oncology, Department of Internal Medicine (SAP, JWL, RSH, JSK) and Translational Research Program (RSH, JSK), Yale Comprehensive Cancer Center, Departments of Pathology and Medical Oncology (JP), Yale School of Medicine, New Haven, CT; Yale Center for Genome Analysis, Yale University, Orange, CT (FLG).
Francesc López-GiráldezSection of Medical Oncology, Department of Internal Medicine (SAP, JWL, RSH, JSK) and Translational Research Program (RSH, JSK), Yale Comprehensive Cancer Center, Departments of Pathology and Medical Oncology (JP), Yale School of Medicine, New Haven, CT; Yale Center for Genome Analysis, Yale University, Orange, CT (FLG).
Roy S HerbstSection of Medical Oncology, Department of Internal Medicine (SAP, JWL, RSH, JSK) and Translational Research Program (RSH, JSK), Yale Comprehensive Cancer Center, Departments of Pathology and Medical Oncology (JP), Yale School of Medicine, New Haven, CT; Yale Center for Genome Analysis, Yale University, Orange, CT (FLG).
Ja Seok KooSection of Medical Oncology, Department of Internal Medicine (SAP, JWL, RSH, JSK) and Translational Research Program (RSH, JSK), Yale Comprehensive Cancer Center, Departments of Pathology and Medical Oncology (JP), Yale School of Medicine, New Haven, CT; Yale Center for Genome Analysis, Yale University, Orange, CT (FLG). jpeter.koo@yale.edu.
Yale Cancer Center · US

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Personalizing NSCLC Therapy: Exploiting KRAS activated pathwaysR01CA155196 · NCI · YALE UNIVERSITY · PI HERBST, ROY S, PAPADIMITRAKOPOULOU, VASSILIKI · 2011 to 2015
$2.8M
Role of CREB in Lung Cancer DevelopmentR01CA126801 · NCI · YALE UNIVERSITY · PI KOO, JA SEOK · 2010 to 2014
$1.6M
NCI NIH HHS 5R01CA155196NCI NIH HHS CA-16359NCI NIH HHS R01 CA126801NCI NIH HHS R01-CA126801NCI NIH HHS R01 CA155196
6 · The paper itself

Abstract

backgroundThe E2F members have been divided into transcription activators (E2F1-E2F3) and repressors (E2F4-E2F8). E2F8 with E2F7 has been known to play an important physiologic role in embryonic development and cell cycle regulation by repressing E2F1. However, the function of E2F8 in cancer cells is unknown.

methodsE2F8 expression was assessed by immunoblotting or immunofluorescence staining in human lung cancer (LC) cells and tissues from LC patients (n = 45). Cell proliferation, colony formation, and invasion analysis were performed to evaluate the role of E2F8 in LC. Microarray analysis was used to determine the target genes of E2F8. The regulation of E2F8 on the expression of ubiquitin-like PHD and RING domain-containing 1 (UHRF1), one of E2F8 target genes, was determined using chromatin immunoprecipitation and promoter activity assays. Human LC xenograft models were used to determine the effects of inhibiting E2F8 by siRNAs (n = 7 per group) or antisense morpholino (n = 8 per group) on tumor growth. Survival was analyzed using the Kaplan-Meier method and group differences by the Student's t test. All statistical tests were two-sided.

resultsLC tumors overexpressed E2F8 compared with normal lung tissues. Depletion of E2F8 inhibited cell proliferation and tumor growth. E2F8 knockdown statistically significantly reduced the expression of UHRF1 (~60%-70%, P < .001), and the direct binding of E2F8 on the promoter of UHRF1 was identified. Kaplan-Meier analysis with a public database showed prognostic significance of aberrant E2F8 expression in LC (HR = 1.91 95% CI = 1.21 to 3.01 in chemo-naïve patients, P = .0047).

conclusionsWe demonstrated that E2F8 is overexpressed in LC and is required for the growth of LC cells. These findings implicate E2F8 as a novel therapeutic target for LC treatment.

Indexed as

AnimalsAntineoplastic AgentsCCAAT-Enhancer-Binding ProteinsCell Line, TumorCell ProliferationCell SurvivalChromatin ImmunoprecipitationFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansImmunoblottingKaplan-Meier EstimateLung NeoplasmsMiceMolecular Targeted TherapyNeoplastic Stem CellsAntineoplastic AgentsCCAAT-Enhancer-Binding ProteinsE2F8 protein, humanRepressor ProteinsUbiquitin-Protein LigasesUHRF1 protein, human

Identifiers

PMID26089541
PMCPMC4651101
OpenAlexW2121271487

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.